Acquisition of major, state-of-the-art instrumentation should ideally have a positive impact on scientists comprising a wide range of disciplines. To achieve such an outcome, The University of Pittsburgh proposes herein to equip a core spectrometric facility at the Center for Environmental and Occupational Health and Toxicology (CEOHT) with a 400 MHz nuclear magnetic resonance (NMR) spectrometer so that investigators can further their respective research ventures. These goals will be realized through the purchase of a spectrometer equipped with state of the art computer software, probes, and electronics. The University will commit supplemental funds to meet the continuing maintenance needs of the instrument (i.e., service contract and cryogenic requirements of the magnet-liquid N2 and He, contracts for He fills). This new instrument is required to meet the demand for NMR time arising from the recent expansion of faculty outside of the Chemistry Department, and will vastly improve the capabilities of not only the CEOHT but also the associated Drug Discovery, Clinical Pharmacology, Radiology and Pharmaceutical Sciences programs. The new NMR spectrometer will accelerate research in the following non-exhaustive list of areas; synthesis and drug discovery of novel microtubule perturbing agents; synthesis and drug discovery of novel adenosine receptor agonists/antagonists structure elucidation of metabolites from expressed cytochrome P450; liposomal drug delivery systems; kinetics of trans- thiocarbamoylation reactions in asthmogen/immunogen elucidation experiments; kinetics of receptor/active site and strength of binding studies involving dual ligands; characterization of multiply-stable- isotope-labelled internal standards of isotope dilution mass spectrometric quantitation schemes; development of novel PET imaging agents, and structure elucidation of natural products isolated by bioactivity-guided fractionation. The new spectrometer will be equipped with probe(s) and channels for 1H, 13C, 15N/19F, 31P and inverse detection, frequency control units for transmitters, variable temperature capability, Z-gradient capability, digital lock, 2H preamplifier for lock and 2H observe, SGI O2 host computer, and a 1H/13C microprobe for less than or equal to mu mol amounts of analytes. This spectrometer will replace the current, 17-year old 200 MHz system, which is now both obsolete and unreliable.